Malaria is endemic in 93 third world countries, with an estimated 198 million malaria cases being reported annually (http://www.who.int/malaria/media/world_malaria_report_2014/en/) and resulting in about 367,000-755,000 deaths per year. About 90% of deaths due to malaria occur in Sub-Saharan Africa, and children under the age of 5 years account for more than 70% of these deaths.
Chloroquine and its derivatives and the arternisinins are the main drugs for treating malaria, but global resistance to these drugs is on the increase. For example, chloroquine-resistant strains of Plasmodium falciparum (the malaria parasite responsible for most malaria cases) have spread to most malaria areas. There have also been reports of field strains of P. falciparum demonstrating in vitro resistance to the artemisinins.
There is therefore an urgent need for an alternative treatment for malaria, especially a last resort antimalarial drug for treating patients (mostly children) with advanced resistant malaria.
Cyclic decapeptides such as the tyrocidines and gramicidin S (i.e. peptides with 10 amino acids forming a ring) are known to have potent antiplasmodial activity. The closely-related tryptocidines and phenycidines, which are cyclic decapeptides with a similar structure, also fall within this group. However, the cyclic decapeptides are considered to be unsuitable for antimalarial treatment as they are haemolytic. Although having a 10-300 fold selectivity towards infected red blood cells, they also lyse healthy red blood cells and other cells, even at micromolar peptide concentrations. They are therefore toxic, especially in a systemic method of treatment.